Protein cleavage by x-ray generated hydroxyl radicals is much more difficult, than nucleic acid cleavage, occurring on timescales 10 x longer. Thus, it is not immediately apparent that these methods will be a boon to time resolved folding studies. However, they can identify solvent accessible regions in unusual pH states or where other (generally enzymatic) cleavage methods fail. Of longer term significance is our preliminary observations that substantial modification, revealed by mass spectrometry, occurs to the native protein after 50-150 milliseconds of exposure to the x-ray beam. For apomyoglobin, these modifications are revealed as a widening of the peak of the native protein in Matrix-Assisted Laser Desorption Time-of-Flight mass spectrometry methods. Electrospray-quadoupole MS, has identified variants with single modifications after only 150 ms exposure to the x-ray beam. These are currently being analyzed by enzymatic digest to pinpoint the regions of modification, which will then become reliable markers of folding processes or protein-protein interactions, and possible open up and entirely new avenue for footprinting research.